The long-term objective of this proposal is to characterize the regulation of microtubule synthesis, polymerization, and function in the hepatocyte so as to better understand their effect on hepatic vesicular transport processes. Specific aims include characterization of the role of microtubules in several hepatocyte vesicular transport processes; definition of the morphologic relationship and interactions between microtubules, other cytoskeletal elements, and transport vesicles; and characterization of the physiologic factors that influence the "up" and "down" regulation of tubulin (the major microtubule protein) synthesis and polymerization in the hepatocyte. The effects of various hormones, the effects of the aging process, and the effects of experimentally induced cholestasis on microtubule dynamics will be explored in detail, in the hope that this work may help explain the pathogenesis of changes in hepatic transport seen with aging, cholestasis, and other disease states.